Research done in vitro has shown that GLP-1 is mildly insulinomimetic in both fat and muscle. We did a study in non-obese (i.e. normal glucose uptake and therefore not resistant to insulins actions ) subjects (published J. Clin. Endocrinol. Metab., 83:2399-2405,1998) with intravenous GLP-1 and could not demonstrate this phenomenon. To do this we used state-of-the-art methodology using tritiated glucose to study glucose output and uptake by the liver. However, as the subjects were young with perfectly normal insulin action we may not have been able to show subtle insulinomimetic actions. We therefore initiated a study in obese, non diabetic (insulin resistant, with normal fasting blood glucose) subjects to see if GLP-1 would decrease resistance to insulin. We finished the study in 12 subjects whose BMI was >30. We are presently analyzing all the data and it does appear that GLP-1 is indeed insulinomimetic (i.e. augments insulin action) in obese people. It also appears to suppress formation of non-esterified fatty acids more than does insulin alone. This tells us that a GLP-1 like compound, such as GLP-1 itself or exendin-4, might not only be useful in diabetes, but also in glucose intolerance. Treatment options that are presently available for type 2 diabetes are less than perfect. The vast majority of type 2 diabetic subjects require insulin at some point in their lives because of deteriorating beta cell function. Project Number Z01AG00214-08 LCI has shown that continuous GLP-1 treatment improves glucose tolerance and increases the rate of beta cell turnover in rodents. GLP-1, given subcutaneously to humans before each meal, does lower blood sugar. But blood sugar levels rise again before the next bolus. We wished to see if GLP-1 given continuously subcutaneously would normalize and maintain a normal blood sugar. We have, therefore, initiated a study whereby GLP-1 is given continuously subcutaneously, via a Mini-Med pump (a small pump about the size of a beeper) to Type 2 diabetic subjects for 48 hours. We then investigate for insulin- secretory capacity and insulin sensitivity. Data from 5 subjects already completed shows that GLP-1 given in this manner can normalize blood sugars. - GLP-1, Glucose uptake, Insulinotropic, Insulinomimetic, BMI, Humans - Human Subjects